INDIANAPOLIS, March 9, 2011 (GLOBE NEWSWIRE) -- Semafore Pharmaceuticals announced today that preclinical data in B-cell malignancies for the company's lead product candidate SF1126 will be presented at the 102nd Annual Meeting of the American Association for Cancer Research (AACR), to be held April 2-6, 2011, in Orlando, FL. SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of all Class I phosphatidylinositol 3-kinase (PI3K) isoforms, mammalian target of rapamycin (mTOR), the proto-oncogene PIM-1, and other cancer-specific kinase targets.
The preclinical studies being presented serve as translational support for ongoing clinical investigation of SF1126 alone and in combination with rituximab in certain B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL), indolent non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), which is currently being conducted at the Arizona Cancer Center. The preclinical studies being presented also include a head-to-head comparison between SF1126 and the clinical-stage, delta isoform-selective PI3K inhibitor (CAL-101) with regard to inducing apoptosis and inhibiting cell proliferation in DLBCL cell lines.
The following poster will be presented in Exhibit Hall A4-C on Tuesday, April 5th, 2011, from 1:00 pm – 5:00 pm Eastern Time:
| Title: | Translational studies of the novel prodrug PI3K/mTOR/PIM1 inhibitor SF1126 in DLBCL |
| Abstract number: | LB-383 |
| Poster Session: | Late-Breaking Research; Experimental and Molecular Therapeutics 2 |
| Location: | Hall A4-C, Poster Section 39 |
| Senior author: | Daruka Mahadevan, MD, Ph.D., Arizona Cancer Center, University of Arizona, Tucson, AZ |
A copy of the above abstract will be available for viewing on-line through the AACR 2011 Meeting website at: http://www.aacr.org/
About SF1126 and the PI3K Pathway
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is vital to several essential biological processes, such as cell growth, survival, motility, and metabolism. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. However, the role of PI3K in a wide range of normal biologic processes raises potential concerns about its inhibition in non-cancerous tissues.
As the only PI3K/mTOR inhibitor prodrug currently in development, Semafore's SF1126 product candidate is designed to overcome these concerns by accumulating preferentially in tumor tissue in an attempt to maximize efficacy and minimize toxicity. SF1126 is a peptidic prodrug that converts to LY294002, one of the most widely studied dual PI3K/mTOR inhibitors that historically suffered from poor solubility. LY294002 is conjugated to an Arg-Gly-Asp (RGD) peptide via a cleavable linker to form SF1126, which has improved properties for clinical use. As a prodrug with improved solubility and site selectivity due to targeting of RGD-recognizing integrin receptors, SF1126 opened up a new avenue for the clinical development of LY294002.
To date, nearly 50 patients with solid tumors or hematological malignancies have been treated with SF1126 in Phase I trials. Administration of SF1126 at doses ranging from 90 to 1,110 mg/m2 has been generally well tolerated with the most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, and fatigue. In November 2010, the U.S. Food and Drug Administration granted orphan drug designation to Semafore's SF1126 product candidate for the treatment of B-cell chronic lymphocytic leukemia (CLL).
About Semafore Pharmaceuticals
Semafore Pharmaceuticals is a private, clinical-stage biotechnology company dedicated to the discovery and development of novel small molecule signal transduction inhibitors targeting the phosphoinositide-3-kinase (PI3K) pathway for the treatment of cancer and other serious diseases. In addition to SF1126, the Company is developing SF2626, a next-generation dual MEK/PI3K inhibitor that is designed to simultaneously inhibit an additional key pathway critical to cancer progression using a single molecule. For more information see the company's web site at www.semaforepharma.com.